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Biomedical subjects

C Yu

Publications and source records attributed to C Yu.

At least 109 records · Page 6Linked to original sources
PubMed2000

ABC-me: a novel mitochondrial transporter induced by GATA-1 during erythroid differentiation.

Transcription factor GATA-1 is essential for normal erythropoiesis. GATA-binding sites are consistently found in promoters or enhancers of genes expressed selectively in erythroid cells. To discover novel GATA-1-regulated genes, we searched for GATA-1-activated transcripts in G1E cells, an erythroid line derived from GATA-1(-) embryonic stem cells. By subtractive analysis, we identified a new ATP-binding cassette (ABC) transporter that is strongly and rapidly induced by GATA-1. This protein, named ABC-me (for ABC-mitochondrial erythroid), localizes to the mitochondrial inner membrane and is expressed at particularly high levels in erythroid tissues of embryos and adults. ABC-me is induced during erythroid maturation in cell lines and primary hematopoietic cells, and its overexpression enhances hemoglobin synthesis in erythroleukemia cells. The ABC proteins participate in diverse physiological processes by coupling ATP hydrolysis to the transport of a variety of substrates across cell membranes. We speculate that ABC-me, a newly identified erythroid-expressed ABC superfamily member, may mediate critical mitochondrial transport functions related to heme biosynthesis.

ATP-Binding Cassette Transporters↗
PubMed2000

Elevated cholesterol metabolism and bile acid synthesis in mice lacking membrane tyrosine kinase receptor FGFR4.

Heparan sulfate-regulated transmembrane tyrosine kinase receptor FGFR4 is the major FGFR isotype in mature hepatocytes. Fibroblast growth factor has been implicated in the definition of liver from foregut endoderm where FGFR4 is expressed and stimulation of hepatocyte DNA synthesis in vitro. Here we show that livers of mice lacking FGFR4 exhibited normal morphology and regenerated normally in response to partial hepatectomy. However, the FGFR4 (-/-) mice exhibited depleted gallbladders, an elevated bile acid pool and elevated excretion of bile acids. Cholesterol- and bile acid-controlled liver cholesterol 7alpha-hydroxylase, the limiting enzyme for bile acid synthesis, was elevated, unresponsive to dietary cholesterol, but repressed normally by dietary cholate. Expression pattern and cholate-dependent, cholesterol-induced hepatomegaly in the FGFR4 (-/-) mice suggested that activation of receptor interacting protein 140, a co-repressor of feed-forward activator liver X receptor alpha, may mediate the negative regulation of cholesterol- and bile acid-controlled liver cholesterol 7alpha-hydroxylase transcription by FGFR4 and cholate. The results demonstrate that transmembrane sensors interface with metabolite-controlled transcription networks and suggest that pericellular matrix-controlled liver FGFR4 in particular may ensure adequate cholesterol for cell structures and signal transduction.

Animals↗
PubMed2000

Adoptive immunotherapy in canine mixed chimeras after nonmyeloablative hematopoietic cell transplantation.

Development of nontoxic and nonmyeloablative regimens for allogeneic hematopoietic stem-cell transplantation will decrease transplantation-related mortality caused by regimen-related toxic effects. In pursuit of this goal, a dog model of stable mixed hematopoietic chimerism was established in which leukocyte-antigen-identical litter mates are given sublethal total-body irradiation (2 Gy) before stem-cell transplantation and immunosuppression with mycophenolate mofetil and cyclosporine afterward. In the current study, we examined whether donor lymphocyte infusion (DLI) could be used as adoptive immunotherapy to convert mixed to complete donor chimerism. First, 8 mixed chimeras were given unmodified DLI between day 36 and day 414 after stem-cell transplantation. After a 10- to 47-week follow-up period, there were no significant changes in the percentage of donor engraftment. Next, we immunized the donor to the minor histocompatibility antigens (mHA) of the recipient by means of repeated skin grafting. Lymphocytes from the mHA-sensitized donor were infused between day 201 and day 651 after transplantation. All 8 recipients of mHA-sensitized DLI had conversion to greater than 98% donor chimerism within 2 to 12 weeks of the infusion. Complications from mHA-sensitized DLI included graft-versus-host disease in 2 dogs and marrow aplasia in 1. These results showed that the low-dose transplant regimen establishes immune tolerance, and mHA-sensitized DLI is required to break tolerance, thereby converting mixed to complete donor chimerism. We propose that mixed chimerism established after nonmyeloablative allogeneic stem-cell transplantation provides a platform for adoptive immunotherapy that has clinical potential in the treatment of patients with malignant diseases.

Animals↗
PubMed2000

Molecular cytogenetic analysis of eight inversion duplications of human chromosome 13q that each contain a neocentromere.

Neocentromeres are fully functional centromeres that have arisen in previously noncentromeric chromosomal locations on rearranged chromosomes. The formation of neocentromeres results in the mitotic stability of chromosomal fragments that do not contain endogenous centromeres and that would normally be lost. Here we describe a unique collection of eight independent patient-derived cell lines, each of which contains a neocentromere on a supernumerary inversion duplication of a portion of human chromosome 13q. Findings in these patients reveal insight into the clinical manifestations associated with polysomy for portions of chromosome 13q. The results of FISH and immunofluorescent analysis of the neocentromeres in these chromosomes confirm the lack of alpha-satellite DNA and the presence of CENtromere proteins (CENP)-C, -E, and hMAD2. The positions of the inversion breakpoints in these chromosomes have been placed onto the physical map of chromosome 13, by means of FISH mapping with cosmid probes. These cell lines define, within chromosome 13q, at least three distinct locations where neocentromeres have formed, with five independent neocentromeres in band 13q32, two in band 13q21, and one in band 13q31. The results of examination of the set of 40 neocentromere-containing chromosomes that have thus far been described, including the 8 neocentromere-containing chromosomes from chromosome 13q that are described in the present study, suggest that chromosome 13q has an increased propensity for neocentromere formation, relative to some other human chromosomes. These neocentromeres will provide the means for testing hypotheses about sequence requirements for human centromere formation.

Aneuploidy↗
PubMed2000

Beta versus gamma for catheter-based intravascular brachytherapy: dosimetric perspectives in the presence of metallic stents and calcified plaques.

PURPOSE: Both beta and gamma emitters are currently used in the catheter-based intravascular brachytherapy. The dosimetric effects due to the presence of metallic stents and calcified plaques have not been fully addressed. This work compares these effects for two most commonly used beta and gamma sources ( (90)Sr and (192)Ir). MATERIALS AND METHODS: An EGS4 Monte Carlo package was used to calculate dose in water for a (90)Sr (supplied by NOVOSTE) and an (192)Ir (Supplied by BEST) source, with or without the presence of a calcified plaque or a metallic stent. Plaques of different shape (shell and disk), size and density, and two types of stainless-steel stents (ring or mesh stent) were studied. The ring stent consists of identical rings stacked along the long axis of the sources. The gap between two rings is 0.3 mm. The mesh stents are made of identical square (0.1 x 0.1 or 0.2 x 0.2 mm(2)) holes separated from each other by stainless-steel wire. The cross section of wire for both ring and mesh stents is 0.1 x 0.1 mm(2). A dose perturbation factor (DPF), defined as the ratio of the doses with and without the presence of a plaque or a stent, was introduced to quantify the effects. A carefully chosen set of EGS4 transport parameters for the small geometry in question was used in the calculation. RESULTS: The radial and axial dose distributions calculated in water were found to agree with the published measurements to within 3%. The dose perturbations due to the presence of calcified plaques or metallic stents were found far more significant for the (90)Sr source than those for the (192)Ir source. Up to 30% dose reduction behind a plaque were observed for the (90)Sr source, while the dose reduction for the (192)Ir source was found to be negligible. The dose enhancement inside a plaque was as high as 10% for the beta source or 6% for the gamma source. In the presence of a stent, the DPF was in the range of 1.15-0.75 for the beta source, while it was almost equal to 1.0 for the gamma source. CONCLUSION: The dose perturbation due to the presence of a calcified plaque or a metallic stent is significant for the beta source. The dose reduction in the region beyond a plaque or a stent could be more than 20%. For the gamma source, the dose effect behind a plaque or a stent is practically negligible. These dosimetric differences between the beta and gamma sources in the presence of a calcified plaque or metallic stent should be considered in the dose prescription of intravascular brachytherapy.

Beta Particles↗
PubMed2000

Cytotoxic T lymphocyte antigen 4-immunoglobulin fusion protein combined with methotrexate/cyclosporine as graft-versus-host disease prevention in a canine dog leukocyte antigen-nonidentical marrow transplant model.

BACKGROUND: We studied whether blocking of the T cell costimulatory signal from B7-->CD28 by cytotoxic T lymphocyte antigen 4-immunoglobulin fusion protein would, either by itself or when added to methotrexate/cyclosporine, result in improved graft-versus-host disease prevention after dog leukocyte antigen nonidentical canine hematopoietic stem cell transplantation after 920 cGy total body irradiation. RESULTS AND CONCLUSIONS: Survivals of cytotoxic T lymphocyte antigen 4-immunoglobulin fusion protein-treated dogs were only slightly prolonged over controls. It appeared that the addition of cytotoxic T lymphocyte antigen 4-immunoglobulin fusion protein failed to induce graft-host tolerance in this model beyond that achieved with methotrexate/cyclosporine alone.

Abatacept↗
PubMed2000

Role of Niemann-Pick type C1 protein in intracellular trafficking of low density lipoprotein-derived cholesterol.

Niemann-Pick type C (NPC) is a disease that affects intracellular cholesterol-trafficking pathways. By cloning the hamster ortholog of NPC1, we identified the molecular lesions in two independently isolated Chinese hamster ovary cell mutants, CT60 and CT43. Both mutants lead to premature translational terminations of the NPC1 protein. Transfecting hamster NPC1 cDNA complemented the defects of the mutants. Investigation of the CT mutants, their parental cells, and an NPC1-stable transfectant allow us to present evidence that NPC1 is involved in a post-plasma membrane cholesterol-trafficking pathway. We found that the initial movement of low density lipoprotein (LDL)-derived cholesterol to the plasma membrane (PM) did not require NPC1. After reaching the PM and subsequent internalization, however, cholesterol trafficking back to the PM did involve NPC1. Both LDL-derived cholesterol and cholesterol originating from the PM accumulated in a dense, intracellular compartment in the CT mutants. Cholesterol movement from this compartment to the PM or endoplasmic reticulum was defective in the CT mutants. Our results functionally distinguish the dense, intracellular compartment from the early endocytic hydrolytic organelle and imply that NPC1 is involved in sorting cholesterol from the intracellular compartment back to the PM or to the endoplasmic reticulum.

Amino Acid Sequence↗
PubMed2000

Transport and pharmacological properties of nine different human Na, K-ATPase isozymes.

Na,K-ATPase plays a crucial role in cellular ion homeostasis and is the pharmacological receptor for digitalis in man. Nine different human Na,K-ATPase isozymes, composed of 3 alpha and beta isoforms, were expressed in Xenopus oocytes and were analyzed for their transport and pharmacological properties. According to ouabain binding and K(+)-activated pump current measurements, all human isozymes are functional but differ in their turnover rates depending on the alpha isoform. On the other hand, variations in external K(+) activation are determined by a cooperative interaction mechanism between alpha and beta isoforms with alpha2-beta2 complexes having the lowest apparent K(+) affinity. alpha Isoforms influence the apparent internal Na(+) affinity in the order alpha1 > alpha2 > alpha3 and the voltage dependence in the order alpha2 > alpha1 > alpha3. All human Na,K-ATPase isozymes have a similar, high affinity for ouabain. However, alpha2-beta isozymes exhibit more rapid ouabain association as well as dissociation rate constants than alpha1-beta and alpha3-beta isozymes. Finally, isoform-specific differences exist in the K(+)/ouabain antagonism which may protect alpha1 but not alpha2 or alpha3 from digitalis inhibition at physiological K(+) levels. In conclusion, our study reveals several new functional characteristics of human Na,K-ATPase isozymes which help to better understand their role in ion homeostasis in different tissues and in digitalis action and toxicity.

Animals↗
PubMed2000

Analysis of a commercial preparation of erythromycin estolates by tandem mass spectrometry and high performance liquid chromatography/electrospray ionization tandem mass spectrometry using an ion trap mass spectrometer.

Because of the lack of a UV chromophore and their much smaller abundances in comparison with the major component, the minor components in erythromycin estolate preparations are difficult to analyze by high performance liquid chromatography ultraviolet (HPLC-UV). Tentative assignment of the major and minor components can be achieved with the combination of full scan and ZoomScan using an ion trap mass spectrometer. Tandem mass spectrometry (MS/MS) provided an effective method to quickly identify most components without chromatographic separation, and all the related compounds, except the isobaric pair ECE and PdMeEA, could be identified in this way. The best result was obtained by using liquid chromatography/tandem mass spectrometry (LC/MS/MS) operated in selected reaction monitoring mode. The major compound, the estolate of erythromycin A (EAE), and seven other minor components, could be separated and identified, with semiquantitative estimates of relative concentrations.

Anti-Bacterial Agents↗
PubMed2000

Towards stationary phases for chromatography on a microchip: molded porous polymer monoliths prepared in capillaries by photoinitiated in situ polymerization as separation media for electrochromatography.

Photoinitiated free radical polymerization has been used for the preparation of porous polymer monoliths within UV transparent fused silica capillaries and quartz tubes. These formats were used as models for the preparation of the separation media within channels of microfabricated devices. A mixture of ethylene dimethacrylate, butyl methacrylate, and 2-acrylamido-2-methyl-1-propanesulfonic acid was polymerized in the presence of a porogenic solvent consisting of 1-propanol, 1,4-butanediol, and water at room temperature under UV irradiation. Modification of the porogen composition enables the tailoring of pore size within the broad range from ca. 100 to 4000 nm. Scanning electron micrographs confirmed the homogeneity of the porous structure of the materials prepared, even in a quartz tube with a diameter as large as 4 mm. Separation properties of the resulting capillary columns were tested in capillary electrochromatography (CEC) mode using a mixture of thiourea and eight aromatic compounds. Plate number as high as 210 000 plates/m were found for a capillary column with optimized porous properties. The monolithic columns were also able to separate mixtures of peptides.

Animals↗
PubMed2000

Expression of collagen type I, II and III in loose body of osteoarthritis.

The expression of collagen type I, II, and III was investigated to evaluate phenotypic change in chondrocytes in loose bodies related to osteoarthritis. We assessed collagen type I, II, and III production in loose bodies from knee joints of ten osteoarthritic patients, using an immunohistochemical method with monoclonal antibodies. Collagen type III expression was identified in all ten loose bodies and was mainly located in cartilage, including chondrocytes and matrices, as well as in a layer of fibroid tissue on the surface. No positive signal for collagen type III was observed in necrotic osteocytes. There was weakly positive staining for collagen type I in chondrocytes. No positive staining for collagen type II could be seen in the cartilage of loose bodies. Cartilage from the non-osteoarthritic knee joints of four people was negative for the expression of collagen type I and III, and positive for the expression of collagen type II. Collagen type I and III expression suggested the dedifferentiation status of chondrocytes in loose bodies.

Adult↗
PubMed2000

Fusion induced aggregation of model vesicles studied by dynamic and static light scattering.

Membrane fusion is a key step in the virus mediated cell fusion. The vesicular dispersion serves as a model system to study the membrane fusion. We employed dynamic and static light scattering to study the fusion of phosphatidylcholine vesicles in the presence of model fusion peptide fragments from the hemagglutinin HA2 protein. The fusion-induced aggregation under the present experimental setup exhibited strong pH dependence, similar to the parental viral protein. Replacement of the glycine residue at the extreme amino terminus by glutamic acid (G1E) abolished fusion activity. The average molecular mass and diameter of vesicular dispersion obtained from static and dynamic light scattering measurements respectively at neutral and acidic pH showed about three fold increase in acidic solution containing wild type fusion peptide. The light scattering data are consistent with lipid mixing results. The present work demonstrates the utility of light scattering as a facile means to monitor the fusion process.

Amino Acid Sequence↗
PubMed2000

Genetic strategies to enhance penicillin acylase production in Escherichia coli.

We demonstrated the improvement of penicillin acylase (PAC) production by optimization of the host/vector system using genetic engineering strategies. Several expression plasmids with improved efficiency for the transcription of the pac gene and/or translation of the pac mRNA were constructed. Mutant strains, isolated by a novel screening method, were effective for use as the expression host to produce PAC. The feasibility of using the mutant strains harboring a selection of expression plasmids for the production of PAC was evaluated. The effect of the mutation(s) resulting in the improved PAC producing ability was characterized. While the production of PAC was significantly enhanced using the optimized host/vector system, the formation of PAC inclusion bodies was shown to be another step limiting the production of recombinant PAC.

Journal Article↗
PubMed2000

Evidence for migration of donor bone marrow stromal cells into recipient thymus after bone marrow transplantation plus bone grafts: A role of stromal cells in positive selection.

Intrathymic T-cell differentiation is characterized by two selection events: positive and negative selection. It has been shown that thymic epithelial cells in the cortex are involved in the positive selection, while macrophages and dendritic cells, derived from hemopoietic stem cells, are involved in the negative selection. Here we investigate whether donor-derived bone marrow stromal cells can migrate into the thymus and participate there in positive selection after bone marrow transplantation plus bone grafts (to recruit bone marrow stromal cells). Allogeneic bone marrow transplantation with or without bone grafts was carried out in the [C57BL/6-->C3H] combination. Fluorescence-activated cell sorter analyses of recipient thymic adherent cells showed that donor-type bone marrow stromal cells exist in the thymus of mice that received bone marrow plus bone grafts but not in the mice that received bone marrow cells alone. Histological examination using confocal microscopy also confirmed the existence of donor-type stromal cells in the thymus of mice that received bone marrow cells plus bones. Both T-cell proliferation and plaque-forming cell assays indicated that the T cells of such mice show donor-type major histocompatibility complex-restriction. These findings strongly suggest that stromal cells can migrate from the bone marrow to the thymus, where they participate in the positive selection of thymocytes.

Animals↗
PubMed2000

Fetal renal volume in normal gestation: a three-dimensional ultrasound study.

To establish a reference chart of fetal kidneys in normal pregnancy, we performed a prospective and cross-sectional study. A total of 152 singleton fetuses ranging between 20 and 40 weeks' gestation and meeting the criteria of normal pregnancies were included. Three-dimensional ultrasound (3-D US) was used to measure the fetal renal volume. Our results revealed that both renal volumes are highly correlated with the fetal gestational age. Using gestational age (GA) as the independent variable and right renal volume (RRV) as the dependent variable, the best-fit regression equation was RRV (mL)=0.74053xGA (week)-13.318 (r = 0.89, p < 0.001). Similarly, the best-fit equation for the left renal volume (LRV) was LRV (mL)=0. 76093xGA (week)-13.421 (r = 0.86, p < 0.001). The normal growth centiles of both kidneys were established based on these two equations. There were no significant differences of the volumes between bilateral kidneys. In conclusion, our data of fetal renal volumes assessed by 3-D US may serve as a reference in evaluating fetal renal growth.

Cross-Sectional Studies↗
PubMed2000

Hereditary haemorrhagic telangiectasia: hepatic lesions demonstrated with colour Doppler and power Doppler sonography.

Visceral vascular abnormalities in patients with hereditary haemorrhagic teleangiectasia (HHT) include teleangiectasis, arteriovenous fistula (AVF), and aneurysms. Sonographic findings and colour Doppler ultrasound (CDU) features of HHT in the liver have been described in a few reports. Presented here is the CDU finding of liver with HHT involvement in two patients, aged 52 and 29 years, respectively. Power Doppler sonography was also performed in the first patient in whom both CDU and power Doppler sonography could demonstrate the abnormal vascular channels in the liver. In the second patient, aneurysms in the left hepatic lobe and of the splenic artery were noted. Angiography was performed in both patients and confirmed the abnormal vascular lesions demonstrated by CDU and/or power Doppler sonographic findings.

Adult↗
PubMed2000

Substituted benz[a]acridines and benz[c]acridines as mammalian topoisomerase poisons.

Coralyne and several other synthetic benzo[a,g]quinolizium derivatives related to protoberberine alkaloids have exhibited activity as topoisomerase poisons. These compounds are characterized by the presence of a positively charged iminium group, which has been postulated to be associated with their pharmacological properties. The objective of the present study was to devise stable noncharged bioisosteres of these compounds. Several similarly substituted benz[a]acridine and benz[c]acridine derivatives were synthesized and their relative activity as topoisomerase poisons was determined. While the benz[c]acridine derivatives evaluated as part of this study were devoid of topoisomerase poisoning activity, several dihydrobenz[a]acridines were able to enhance DNA cleavage in the presence of topo I. In contrast to certain protoberberine derivatives that did exhibit activity as topo II poisons, none of the benz[a]acridines derivatives enhanced DNA cleavage in the presence of topo II. Among the benz[a]acridines studied, 5,6-dihydro-3,4-methylenedioxy-9,10-dimethoxybenz[a]acridine, 13e, was the most potent topo I poison, with comparable potency to coralyne. These data suggest that heterocyclic compounds structurally related to coralyne can exhibit potent topo I poisoning activity despite the absence of an iminium cation within their structure. In comparison to coralyne or other protoberberine derivatives, these benz[a]acridine derivatives possess distinctly different physicochemical properties and represent a novel series of topo I poisons.

Acridines↗